Data from 4 studies show smell, eye tests hold potential to early identify Alzheimer's disease.
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14 July 2014 - Results from four studies, unveiled yesterday at the ongoing Alzheimer's Association International Conference 2014 (AAIC 2014) in Copenhagen, have demonstrated that a reduced ability to identify odours may be indicative of the development of cognitive impairment and Alzheimer's disease, whereas examinations of the eye could show the build-up of beta-amyloid, a protein related to Alzheimer's, in the brain.
The first trial explored the relations between sense of smell, memory performance, biomarkers of loss of brain cell function, as well as amyloid deposition in 215 clinically normal elderly people participating in the Harvard Aging Brain Study at the Massachusetts General Hospital. The study used the 40-item University of Pennsylvania Smell Identification Test (UPSIT) and various cognitive tests, as well as assessed the size of the entorhinal cortex and the hippocampus, both important for memory, and amyloid deposits in the brain.
Results showed that in these participants, a smaller hippocampus and a thinner entorhinal cortex were related to worse smell identification and worse memory. Furthermore, in a subgroup of study population with increased levels of amyloid in their brain, greater brain cell death, as shown by a thinner entorhinal cortex, was markedly related to worse olfactory function, following an adjustment for variables, such as age, gender and an estimate of cognitive reserve.
Matthew E. Growdon, BA, MD/MPH candidate at Harvard Medical School and Harvard School of Public Health, said that these findings indicate a potential role for smell identification testing in clinically normal, older people who are at risk for Alzheimer's disease, and that such testing may be useful to detect suitable candidates for more expensive or invasive tests.
The second study, carried out at Columbia University Medical Center, evaluated a multi-ethnic (34% White, 30% African-American, 36% Hispanic) sample of 1,037 non-demented elderly individuals with an average age of 80.7, and evaluated them in multiple ways at three time periods, including from 2004-2006, 2006-2008, and 2008-2010. UPSIT was performed in English and Spanish participants between 2004 and 2006. During a follow-up period, a total of 109 participants transitioned to dementia (101=Alzheimer's) and 270 deaths were reported.
According to the findings, in 757 participants who were followed, lower odour identification scores on UPSIT were notably related to the transition to dementia and Alzheimer's disease, after controlling for demographic, cognitive and functional measures, language of administration and apolipoprotein E genotype. For each point lower that an individual scored on the UPSIT, the risk of Alzheimer's was elevated by nearly 10%. Moreover, lower baseline UPSIT scores, but not measures of verbal memory, were markedly related to cognitive decline in people without baseline cognitive impairment.
In case additional large-scale trials replicate these findings, a comparatively low-cost test, such as odour identification, may be able to detect individuals at higher risk of dementia and Alzheimer's disease at a very early stage, and may be useful in detecting individuals at elevated risk of cognitive decline more broadly, said Dr. Davangere Devanand, Professor of Psychiatry at Columbia University Medical Center.
Additionally, a third trial, conducted by Australia's CSIRO (Commonwealth Scientific and Industrial Research Organization), Edith Cowan University, McCusker Alzheimer's Research Foundation and US NeuroVision Imaging LLC, included volunteers who received a proprietary supplement comprising curcumin, which binds to beta-amyloid with high affinity and has fluorescent properties enabling amyloid plaques to be identified in the eye using NeuroVision Imaging's system, as well as the retinal amyloid imaging (RAI) technique. Moreover, the participants underwent brain amyloid PET imaging to correlate the retina and brain amyloid accumulation.
Preliminary data for 40 out of the 200 volunteers showed that amyloid levels identified in the retina were notably associated with brain amyloid levels as demonstrated by PET imaging. The retinal amyloid test also distinguished Alzheimer's from non-Alzheimer's individuals with 100% sensitivity and 80.6% specificity. In addition, longitudinal trials on an initial cohort showed an average rise of 3.5% in retinal amyloid over a 3.5-month period, indicating the promise of the technology for monitoring response to treatment. The full trial is set to be wrapped up later in 2014.
Shaun Frost of the CSIRO commented that the researchers see this technique as a potential initial screen that could support brain PET imaging, MRI imaging and clinical tests. In case additional research demonstrates that these initial results are accurate, the technology could become part of a person's regular eye check-up. The high resolution level of the images may further enable precise monitoring of a person's retinal plaques as a potential method to follow progression and response to therapy, Frost added.
Finally, US medical technology company Cognoptix Inc unveiled data from a fourth, Phase II feasibility trial investigating a new fluorescent ligand eye scanning (FLES) system that identifies beta-amyloid in the lens of the eye using a topically-applied ointment binding to amyloid and a laser scanner. The study included 20 individuals with probable Alzheimer's disease, including mild cases, and 20 age-matched healthy volunteers, whose Alzheimer's status was masked from the observers. The ointment was applied to the inside of people's lower eyelids the day prior to assessment. Laser scanning identified beta-amyloid in the eye by the presence of a specific fluorescent signature. All participants underwent brain amyloid PET scanning to assess amyloid plaque density in the brain.
The research team used data from the fluorescent imaging and could distinguish individuals with Alzheimer's from healthy controls with 85% sensitivity and 95% specificity. Furthermore, amyloid levels based on the eye lens test were significantly associated with findings collected through PET brain imaging. There were no serious side effects in the trial.
These findings validate prior Cognoptix data and show the ability of the FLES system to reproduce the results of clinical diagnosis of Alzheimer's with high sensitivity and specificity. The system also demonstrates potential as a method for early detection and monitoring of the disease, said Cognoptix president and chief executive, Paul D. Hartung.
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|Article Type:||Disease/Disorder overview|
|Date:||Jul 14, 2014|
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